MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND INTERLEUKIN-8 PRODUCTION BY RHEUMATOID SYNOVIOCYTES - EFFECTS OF ANTIRHEUMATIC DRUGS
MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND INTERLEUKIN-8 PRODUCTION BY RHEUMATOID SYNOVIOCYTES - EFFECTS OF ANTIRHEUMATIC DRUGS
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DOI：
10.1016/1043-4666(94)90038-8
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发表时间：
1994-03-01
期刊：
影响因子：
3.8
通讯作者：
SEITZ, M
中科院分区：
文献类型：
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作者：
LOETSCHER, P;DEWALD, B;SEITZ, M
在类风湿关节炎(RA)的发病机制中，活化的滑膜细胞是主要的效应细胞，因为它们能够分泌多种炎症介质。在这些介质中，趋化蛋白单核细胞趋化蛋白1(MCP-1)和白介素8(IL-8)可能有助于炎性细胞向关节内的募集。我们检测了抗风湿药物对暴露于促炎激动剂的培养的RA滑膜细胞产生MCP-1和IL-8的影响。两种趋化细胞因子均通过特异性酶联免疫吸附试验(EL ISA)进行定量，并在培养上清液中积累。虽然形成的时间进程相似，但IL-8的产量是MCP-1的3到10倍。非类固醇抗炎药抑制前列腺素的合成，但不影响两种趋化细胞因子的产生和释放。在接受测试的三种疾病修改药物中，地塞米松和硫代马来酸金钠(GST)抑制IL-8和MCP-1的产生，而甲氨蝶呤(MTX)则无效。地塞米松可使滑膜细胞MCP-1和IL-8的合成分别减少20-65%和60-80%，而GST对滑膜细胞MCP-1和IL-8的合成有抑制作用，但对最佳刺激的滑膜细胞无明显影响。综上所述，这些结果表明，MCP-1和IL-8的产生同样受到抗风湿药物的影响，地塞米松是最有效的抑制剂，这表明糖皮质激素的部分抗风湿作用是由于阻止作用于中性粒细胞和单核细胞的趋化细胞因子的积聚。
Activated synoviocytes are major effector cells in the pathogenesis of rheumatoid arthritis (RA) because of their capacity to secrete a variety of inflammatory mediators. Among these mediators, the chemotactic proteins monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) are likely to contribute to the recruitment of inflammatory cells into the arthritic joint. We examined the effects of anti-rheumatic drugs on the MCP-1 and IL-8 production by cultured RA synoviocytes exposed to pro-inflammatory agonists. Both chemotactic cytokines were quantified by specific enzyme-linked immunosorbent assays (ELISA), and found to accumulate in the culture supernatants. Although the time course of formation was similar, the yield of IL-8 was three to 10-fold higher than that of MCP-1. Non-steroidal anti-inflammatory drugs inhibited the synthesis of prostaglandins, but did not influence the production and release of both chemotactic cytokines. Of three disease-modifying drugs tested, dexamethasone and gold sodium thiomalate (GST) inhibited the production of IL-8 and MCP-1, while methotrexate (MTX) was inactive. Dexamethasone reduced the production of MCP-1 and IL-8 by 20–65% and 60–80%, respectively, whilst GST inhibited MCP-1 and IL-8 synthesis in suboptimally, but not in optimally stimulated synoviocytes. Taken together, these results show that the production of MCP-1 and IL-8 is similarly affected by anti-rheumatic drugs and that dexamethasone is the most potent inhibitor suggesting that part of the anti-rheumatic action of glucocorticoids is due to prevention of accumulation of chemotactic cytokines acting on neutrophils and monoctyes.